title: Mitochondrial disorders in NSAIDs-induced small bowel injury.
abstract: Recent studies using small bowel endoscopy revealed that non-steroidal anti-inflammatory drugs including low-dose aspirin, can often induce small bowel injury. Non-steroidal anti-inflammatory drugs-induced small bowel mucosal injury involves various factors such as enterobacteria, cytokines, and bile. Experimental studies demonstrate that both mitochondrial disorders and inhibition of cyclooxygenases are required for development of non-steroidal anti-inflammatory drugs-induced small bowel injury. Mitochondrion is an organelle playing a central role in energy production in organisms. Many non-steroidal anti-inflammatory drugs directly cause mitochondrial disorders, which are attributable to uncoupling of oxidative phosphorylation induced by opening of the mega channel called mitochondrial permeability transition pore on the mitochondrial membrane by non-steroidal anti-inflammatory drugs. Bile acids and tumor necrosis factor-α also can open the permeability transition pore. The permeability transition pore opening induces the release of cytochrome c from mitochondrial matrix into the cytosol, which triggers a cascade of events that will lead to cell death. Therefore these mitochondrial disorders may cause disturbance of the mucosal barrier function and elevation of the small bowel permeability, and play particularly important roles in early processes of non-steroidal anti-inflammatory drugs-induced small bowel injury. Although no valid means of preventing or treating non-steroidal anti-inflammatory drugs-induced small bowel injury has been established, advances in mitochondrial studies may bring about innovation in the prevention and treatment of this kind of injury.
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanigawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nadatani
authors.forename: Koji
authors.initials: K
authors.lastname: Otani
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Machida
authors.forename: Hirotoshi
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authors.lastname: Okazaki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yamagami
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tominaga
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa